A. Overall objectives: 1. To identify B cell line models representing different stages of B cell development which can differentiate or dedifferentiate in appropriate in vivo or in vitro microenvironments. 2. To clarify the cellular and molecular bases for B lymphocyte development. 3. To clarify the relationship between B lymphocyte transformation and B-lymphocyte development. B. Species studies: mice and humans C. Specific Studies: 1. Differential expression of c-myb proto-oncogene mRNA in murine B-cell tumors. Three kinds of approaches have been used (i.e., tumor cell lines, induction of differentiation in a cloned cell line, and somatic cell hybrids). First, expression of the c-myb proto-oncogene has been examined in a series of murine B-cell tumor cell lines. These tumors included examples representative of pre B-cells (4), early and late B-cells (8), and plasma cells (3). The pre B-cell tumors express similar high levels of c-myb mRNA while the B-cell lymphomas and plasmacytomas produce 5-30 fold lower levels. These results indicate that transcription of the c-myb gene decreases during B-cell development. Second, the 70Z/3.12 cell line is a carcinagen induced pre-B-cell tumor that produces a cytoplasmic mu heavy chain.